Diabetes is a strong risk factor for premature and severe stroke. The GLP-1R (glucagon-like peptide-1 receptor) agonist Ex-4 (exendin-4) is a drug for the treatment of T2D (Type 2 diabetes) that may also have neuroprotective effects. The aim of the present study was to determine the efficacy of Ex-4 against stroke in diabetes by using a diabetic animal model, a drug administration paradigm and a dose that mimics a diabetic patient on Ex-4 therapy. Furthermore, we investigated inflammation and neurogenesis as potential cellular mechanisms underlying the Ex-4 efficacy. A total of seven 9-month-old Type 2 diabetic Goto–Kakizaki rats were treated peripherally for 4 weeks with Ex-4 at 0.1, 1 or 5 μg/kg of body weight before inducing stroke by transient middle cerebral artery occlusion and for 2–4 weeks thereafter. The severity of ischaemic damage was measured by evaluation of stroke volume and by stereological counting of neurons in the striatum and cortex. We also quantitatively evaluated stroke-induced inflammation, stem cell proliferation and neurogenesis. We show a profound anti-stroke efficacy of the clinical dose of Ex-4 in diabetic rats, an arrested microglia infiltration and an increase of stroke-induced neural stem cell proliferation and neuroblast formation, while stroke-induced neurogenesis was not affected by Ex-4. The results show a pronounced anti-stroke, neuroprotective and anti-inflammatory effect of peripheral and chronic Ex-4 treatment in middle-aged diabetic animals in a preclinical setting that has the potential to mimic the clinical treatment. Our results should provide strong impetus to further investigate GLP-1R agonists for their neuroprotective action in diabetes, and for their possible use as anti-stroke medication in non-diabetic conditions.

The goal of the study was to assess longitudinal changes in quality of life among patients who screened positive for depression and patients who did not enroll in an outpatient heart failure disease management program (HFDMP). Patients with an ejection fraction ≤40% and clinical signs and symptoms of heart failure were enrolled over 11 months from August 2007 to July 2008. Study participants (n=314) were divided at baseline into "depressed" (9-Question Patient Health Questionnaire [PHQ-9] ≥10) and "nondepressed" (PHQ-9 <10) groups. The two cohort groups had quality of life assessed by the Minnesota Living With Heart Failure Questionnaire at baseline and at 1 year while enrolled in the HFDMP. Both groups showed improved quality of life scores, with the depressed group experiencing a greater mean score decrease (14.4 vs 10.8 for nondepressed patients; P<.01). Both patients who screened positive for depression and those who did not enroll in an HFDMP improved their quality of life scores, with depressed patients experiencing a statistically significant greater mean score reduction (better quality of life).

Background-Little is known about the importation of a heart failure disease management program (HFDMP) into lowand middle-income countries. We examined the feasibility of importing a HFDMP into the country of Georgia, located in the Caucuses. Methods and Results-Patients with ejection fraction Յ40% were enrolled into a prospective, observational study consisting of a new HFDMP staffed by local cardiologists. Medications, emergency department use, hospital admissions, and mortality were assessed by interviews with patients or their families. Screening resulted in 400 patients who were followed for 10.2Ϯ3.5 months. ␤-Blocker prescriptions increased from 7.4 -80.7% (PϽ0.001), angiotensinconverting enzyme inhibitor prescriptions increased from 18.4 -92.6% (PϽ0.001), and mean systolic blood pressure declined from 145 to 114 mm Hg (PϽ0.001). Patients visiting the emergency department and hospitalizations were lowered by 40.7% and 52.5%, respectively, but were also influenced by the outbreak of war, during which 17.5% (nϭ70) of patients received follow-up in refugee tents. All-cause mortality extended to 7% of patients, with 12 of 28 deaths caused by war-related events. Conclusions-Importation of a Western HFDMP was demonstrated to be feasible, with a 5-fold increase in the use of recommended therapies, reduction of blood pressure, decrease of emergency department visits, and hospitalizations for heart failure. These measures could result in substantial cost savings in resource-limited settings, but assessment is complicated in unstable areas. Translating effective interventions to low-and middle-income countries requires sensitivity to regional cultures and flexibility to adapt both clinical goals and strategies to unexpected conditions. (Circ Heart Fail. 2011;4:763-769.)

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